Predictive Role of Microbiome in Patients With Urothelial Carcinoma

This study aims to establish the microbiota composition as a predictive tool for the response to the intravesical immunotherapy with Bacillus Calmette-Guérin (BCG) and 2 different chemotherapies schemes.

In this prospective cohort study patients with low/intermediate/high risk non muscle invasive bladder carcinoma (NMIBC) that undergo BCG/chemo treatment will be enrolled to collect urine stool and blood at different endpoints. Microbiota, short-chain fatty acids and immunophenotype will be quantified to develop a predictive screening platform, which might also integrate traditional urinary cytology and FISH data.

Study Overview

• Status: Not yet recruiting
• Conditions: Urinary Bladder Cancer
• Intervention / Treatment: Other: DNA extraction from urine, stool and biopsy. Isolation of serum and PBMC from peripheral blood.

Detailed Description

The purpose of this research is to understand the possible use of microbial profile from catheterized urine and feces of patients with NMIBC to categorize patients in two groups: those likely to respond positively and those unlikely to respond to the therapy. Goal of this study is to identify the predictive role of the microbiome to therapy response, thus allowing clinicians to deliver the most appropriate treatment based on the microbiome (microbiome-personalized therapy).

• Study Type: Observational
• Enrollment (Estimated): 420

Contacts and Locations

• Study Contact: Name: Massimo Alfano, PhD; Phone Number: 6351 +39-022643; Email: alfano.massimo@hsr.it
• Study Contact Backup: Name: Marco Moschini, MD, PhD; Phone Number: 9742 +39-022643; Email: moschini.marco@hsr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults with diagnosis of NMIBC, both first diagnosis or relapsing NMIBC.

Description

Inclusion Criteria:

• Adults aged ≥ 18 years, all able to signed informed consent form;
• Diagnosis of NMIBC provided by an experience pathology, by using tissue specimens that were staged according to the TNM classification and morphoarchitectural criteria according to the WHO classification.

Exclusion Criteria:

• Participants with ongoing urinary tract infection;
• Antibiotic treatment within the last month;
• Immuno-/chemo- therapy within the past 3 months;
• Chronic immunosuppressive therapy;
• Additional major diagnosis known to affect the gut or bladder microbiota;
• Use of probiotics;
• Uncontrolled diabetes;
• Participants with other malignancy or previous history of oncological or autoimmune diseases.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1M. Predictive role of microbiome in male with low grade NMIBC undergoing Gem/Dox.; Predictive role of microbiome in male with low grade non-muscle invasive bladder carcinoma undergoing Gem/Dox.	Other: DNA extraction from urine, stool and biopsy. Isolation of serum and PBMC from peripheral blood.; DNA extraction from urine, stool and biopsy for microbiome analysis. Isolation of peripheral blood mononuclear cells from peripheral blood for immunophenotypic analysis, and isolation of serum for analysis of cytokines and bacterial metabolites.
1F. Predictive role of microbiome in female with low grade NMIBC undergoing Gem/Dox.; Predictive role of microbiome in female with low grade non-muscle invasive bladder carcinoma undergoing Gem/Dox.	Other: DNA extraction from urine, stool and biopsy. Isolation of serum and PBMC from peripheral blood.; DNA extraction from urine, stool and biopsy for microbiome analysis. Isolation of peripheral blood mononuclear cells from peripheral blood for immunophenotypic analysis, and isolation of serum for analysis of cytokines and bacterial metabolites.
2M. Predictive role of microbiome in male with intermediate grade NMIBC undergoing MMC.; Predictive role of microbiome in male with intermediate grade non-muscle invasive bladder carcinoma undergoing MMC.	Other: DNA extraction from urine, stool and biopsy. Isolation of serum and PBMC from peripheral blood.; DNA extraction from urine, stool and biopsy for microbiome analysis. Isolation of peripheral blood mononuclear cells from peripheral blood for immunophenotypic analysis, and isolation of serum for analysis of cytokines and bacterial metabolites.
2F. Predictive role of microbiome in female with intermediate grade NMIBC undergoing MMC.; Predictive role of microbiome in female with intermediate grade non-muscle invasive bladder carcinoma undergoing MMC.	Other: DNA extraction from urine, stool and biopsy. Isolation of serum and PBMC from peripheral blood.; DNA extraction from urine, stool and biopsy for microbiome analysis. Isolation of peripheral blood mononuclear cells from peripheral blood for immunophenotypic analysis, and isolation of serum for analysis of cytokines and bacterial metabolites.
3M. Predictive role of microbiome in male with high grade NMIBC undergoing BCG.; Predictive role of microbiome in male with high grade non-muscle invasive bladder carcinoma undergoing BCG.	Other: DNA extraction from urine, stool and biopsy. Isolation of serum and PBMC from peripheral blood.; DNA extraction from urine, stool and biopsy for microbiome analysis. Isolation of peripheral blood mononuclear cells from peripheral blood for immunophenotypic analysis, and isolation of serum for analysis of cytokines and bacterial metabolites.
3F. Predictive role of microbiome in female with high grade NMIBC undergoing BCG.; Predictive role of microbiome in female with high grade non-muscle invasive bladder carcinoma undergoing BCG.	Other: DNA extraction from urine, stool and biopsy. Isolation of serum and PBMC from peripheral blood.; DNA extraction from urine, stool and biopsy for microbiome analysis. Isolation of peripheral blood mononuclear cells from peripheral blood for immunophenotypic analysis, and isolation of serum for analysis of cytokines and bacterial metabolites.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish the change of microbial profile in high-grade NMIBC patients after BCG administration	Establish the change of urinary and fecal microbiome richness and diversity, and immunophenotype in bladder carcinoma patients after intravesical BCG treatment.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The predictive role of microbiome in BCG responsiveness	Categorize potential candidates for BCG therapy, based on the microbiota pre-therapy.	11 years

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2035

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: November 4, 2024
• First Posted (Estimated): November 5, 2024

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 4, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell
• Other Study ID Numbers: UROBIOTA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No